As will be mentioned further infra, one of the first discoveries relating to the role of nitric oxide role was arrived at in an attempt to identify the agent responsible for promoting blood vessel relaxation and regulating vascular tone. This agent, endothelium-derived relaxing factor (EDRF), was assumed to be a protein similar to other known signalling molecules. The discovery that EDRF was in fact nitric oxide, a small gaseous molecule—led to additional interest and research in the field.
Nitric Oxide is a very short lived molecule, having a half life of only a few seconds. Nitric Oxide may diffuse rapidly across cell membranes. Furthermore, depending on environmental conditions, Nitric Oxide may act on elements that may be at a distance of several hundred microns from the site of Nitric Oxide production.
Nitric Oxide is produced by enzymes known as nitric oxide synthases of which there are three types—Inducible (iNOS), endothelium (eNOS) and neuronal (nNOS). Each enzyme acts on various target tissues.
A mode of action for Nitric Oxide is to stimulate guanylate cyclase, leading to an increase in intracellular cyclic GMP in target cells. This, in turn, may lead to further effects, depending on the cell.
Nitric Oxide is synthesised from L-arginine by the action of Nitric Oxide synthase (NOS), with the production of L-citrulline. L-Citrulline may then be recycled to L-arginine by argininosuccinate synthetase and argininosuccinase in a cycle that allows it to be reused continuously. However, both oxygen and NADPH are required in order for the recycling process to occur.
The nitric oxide (NO) system has been the subject of much study in recent years, due to the numerous discoveries on its actions and effects in the body.
In 1991, Moncasa et al. indicated that the nitric oxide is produced by the endothelium of blood vessels and assists in the regulation of vascular tone/blood pressure. Then, again in 1991, Snyder and Bredt indicated that nitric oxide was manufactured in many tissues including, but not limited to, the central and peripheral nervous systems.
Later, in 1993, Garthwaite observed that nitric oxide played a role in neural signaling.
In 1999, Marechal and Gailly found that nitric oxide has an important role in mechanical and metabolic muscle power.
Then, in 2003, Narin et al. indicated that regular aerobic exercise may result in an increase in blood concentrations of nitrite oxide. Nitric oxide is thus an important signaling molecule that acts in many tissues and offers a diverse range of physiological processes.
Rector et al. reports that in 1996, patients in a double-blind study having moderate to severe heart failure were given 6 weeks of oral arginine (5.6 to 12.6 g/day) and 6 weeks of matched placebo capsules in random sequence.
In 2001, Nagaya et al. reported that compared with placebo, arginine significantly increased forearm blood flow during forearm exercise. Specifically, patients with primary or precapillary secondary pulmonary hypertension were given a placebo or oral arginine (0.5 g/10 kg or 3.5 g for a 70 kg person) for one week. Arginine was found significantly decreased, versus placebo, the mean pulmonary arterial pressure and pulmonary vascular resistance, indications that arginine causes pulmonary vasodilation.
In another 2001 study, Marchesi et al. evaluated endothelial function (expressed as flow-mediated vasodilation [FMV]) in 7 healthy males. On day one, measurements were made at baseline and 2, 4 and 6 hours after a standardized oral fat load. Arginine (6 g/day) was then given for 10 days and the same measurements were taken an day 11. After the first oral fat load, FMV significantly decreased at 2 and 4 h, and overlapped with the basal levels at 6 h. After arginine treatment, FMV significantly decreased at 2 h and normalized after 4 and 6 h. As such, the authors concluded that postprandial endothelial impairment is partly abolished by arginine administration.
In 2000, Bednarz at al, reported that arginine supplementation increased endurance. For example, 25 patients with stable coronary artery disease underwent two separate exercise tests after they were given a placebo or 6 g oral L-arginine for 3 days. In summary, arginine was found to significantly increased exercise duration.
Then in 1997, Ceremuzynski et al. found that the administration of oral L-arginine (6 g) for 3 days increased exercise capacity in 22 patients with stable angina pectoris and healed myocardial infarction compared
Nitric oxide as it relates to sports performance dilates and opens blood vessels through eNOS enhancement, which allows for a increased transport of nutrients into the cell. Users have reported a “pumped” effect showing that more blood is being drawn into the muscle. This effect, while quite superficial may have implications in numerous sports. As blood flow goes, the amount of nutrients delivered to the tissues impacts numerous aspects of athletic performance, including the rate of protein synthesis, compartmentalization of blood glucose, nutrient partitioning and numerous other pathways.
Nitric Oxide has also become a targeted approach for those looking to enhance lean body mass and exercise performance. Products on the market that claim this benefit contain various forms of L-Arginine.
Arginine has been shown in some research to increase levels of Nitric oxide. However, the doses administered in research are very high, resulting in unwanted side effects. The administration of L-Arginine in the enhancement of nitric oxide is somewhat limited in these aspects. Thus, there is a need for a more viable method and composition for enhancing nitric oxide.